Site-Selective Reaction of Enaminones and Enamine Esters for the Synthesis of Novel Diverse Morphan Derivatives

Abstract

An efficient and concise protocol was developed for the synthesis of diverse morphan derivatives 5-7 by the Michael and aza-Michael reaction of different types of quinone monoketals 1 or quinone imine ketals 2 with enaminones or enamine esters 3 promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene in acetone at reflux. Notably, when cyclic enaminone 4 was used as a substrate in the aza-Michael and 1,2-addition reactions with quinone monoketals 1, they gave another novel morphan 8. This method is suitable for parallel synthesis of bridged ring compounds. As a result, highly diverse morphan derivatives were easily and efficiently prepared by the Michael/aza-Michael or aza-Michael/1,2-addition reactions.

Figure 1

Structures of morphans and the targeted compounds.

Scheme 1. Synthesis Routes of Morphans 5–8

Figure 2

X-ray crystal structure of 5n (left) and 6e (right) (ellipsoids are drawn at the 30% probability level).

Figure 3

X-ray crystal structure of 7b (left) and 8a (right) (ellipsoids are drawn at the 30% probability level).

Scheme 2. Mechanism Hypotheses of the Cascade Reaction